Bottom Line:
GT-Tal was further metabolized to its aglycone, free GT and conjugated GT.Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed.GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.

ABSTRACTThe isoflavonol glycoside Talosin A, genistein (GT)-7-α-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-β-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean C(max) of 2.74 µg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being converted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean C(max) of 0.24 mg/mL at 1.25 h; conjugated GT with a mean C(max) of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.

Mentions:
The plasma concentration-time profiles of total GT-Glu and GT-Tal after oral administration of GT-Glu and GT-Tal are shown in Figs. 1 and 2. The pharmacokinetic parameters for GT-Glu and GT-Tal are summarized in Tables 1 and 2. Free GT-Glu or GT-Tal could not be detected prior to enzymatic hydrolysis of the conjugates after oral administration. GT-Glu was slowly absorbed compared to GT-Tal after being converted into its aglycone and conjugate metabolites (Free-GT, Cmax of 0.24 ± 0.08 µg/mL at 1.25 ± 0.05 h; Conjugated-GT, Cmax of 1.31 ± 0.45 µg/mL at 2.00 ± 0.00 h; Table 1). GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into conjugates of GT-Tal with a Cmax of 2.74 ± 0.93 µg/mL at 0.25 ± 0.00 h (Table 2). It was further metabolized into its aglycone, Free-GT, with a Cmax of 0.24 ± 0.01 µg/mL at 1.00 ± 0.00 h and Conjugated-GT with a Cmax of 0.41 ± 0.25 µg/mL at 0.69 ± 0.38 h (Table 2).

Mentions:
The plasma concentration-time profiles of total GT-Glu and GT-Tal after oral administration of GT-Glu and GT-Tal are shown in Figs. 1 and 2. The pharmacokinetic parameters for GT-Glu and GT-Tal are summarized in Tables 1 and 2. Free GT-Glu or GT-Tal could not be detected prior to enzymatic hydrolysis of the conjugates after oral administration. GT-Glu was slowly absorbed compared to GT-Tal after being converted into its aglycone and conjugate metabolites (Free-GT, Cmax of 0.24 ± 0.08 µg/mL at 1.25 ± 0.05 h; Conjugated-GT, Cmax of 1.31 ± 0.45 µg/mL at 2.00 ± 0.00 h; Table 1). GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into conjugates of GT-Tal with a Cmax of 2.74 ± 0.93 µg/mL at 0.25 ± 0.00 h (Table 2). It was further metabolized into its aglycone, Free-GT, with a Cmax of 0.24 ± 0.01 µg/mL at 1.00 ± 0.00 h and Conjugated-GT with a Cmax of 0.41 ± 0.25 µg/mL at 0.69 ± 0.38 h (Table 2).

Bottom Line:
GT-Tal was further metabolized to its aglycone, free GT and conjugated GT.Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed.GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.

ABSTRACTThe isoflavonol glycoside Talosin A, genistein (GT)-7-α-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-β-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean C(max) of 2.74 µg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being converted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean C(max) of 0.24 mg/mL at 1.25 h; conjugated GT with a mean C(max) of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.